HIV Genetics - a more indepth look at the AIDS virus

Member of the lentivirus family. Other lentiviruses include feline immunodeficiency virus (cats), simian immunodeficiency virus (monkeys), sheep visna virus, and equine infectious anemia (horses). The viruses do not cross species, they are very specific for proteins on the immune cell surfaces. However, coming into contact with other species and viruses can induce mutations that create a new virus capable of infecting another species. HIV is thought to have been born this way, as a mutation of SIV in the jungles of Africa where bushmeat consumption, the eating of wild animals particularly monkeys and apes, occurs.

Variations

There are two major genetic variations, the most common is HIV-1. West Africa has seen its cousin HIV-2. The types of HIV are then classified by groups and further broken down into clades based on geography and transmission. The virus mutates quickly due to low fidelity of the viral polymerase so it is often genetically different in the same person as it progresses through the infection. Most variations occur in the envelope proteins which are what are recognized for vaccination and what make vaccine development difficult. HIV-1 groups: O – outlier M – major, the more common form M clades: designated by letters A through J. examples: B is the most common form in Western Europe and the United States. It grows poorly in dendritic cells. E is the most common in Thailand and spreads predominately via infection of vaginal dendritic cells.

Structure

Each viral molecule carries 2 copies of its RNA genome, reverse transcriptase necessary for integration into the host genome, and enzymes necessary for integrating into the host genome and processing new viral proteins. The RNA is converted to DNA and then translated along with the hosts genome to produce new viral proteins at the expense of the hosts functions. The viral proteins are produced as large inactive precursors that are then cut into their functional parts. It is at this step that pharmaceuticals (antiproteases) act. Some HIV strains have defective genes that affect the clinical course of the disease. Example: nef-defective HIV-1 produces a lower viral load and thus a slower onset of AIDS. The viral molecule has an outer envelope (lipid bilayer) derived from the host cell. The virus coded inner envelope contains viral glycoproteins that are the targets of antibodies used in screening for HIV infection and for infecting host cells. In particular, gp120 and gp41 on the virus surface target CD4 and a necessary coreceptor, CXCR4 on T cells and CCR5 on macrophages. A Scandinavian population with defective CCR5 receptors has shown significant immunity to certain types of HIV infection. The ability of a strain of virus to target particular coreceptors explains the observed tropism, the variations in clades. Infection with multiples types of HIV can lead to a seeming super infection based on cumulative abilities of the viruses to infect various cell types earlier on in the clinical course of the disease.

How infection occurs

The virus molecule binds the receptors, fuses with the host cell membrane, and injects its contents into the host cell thus infecting it. In nondividing cells the virus remains as linear DNA, waiting for the cells to be activated. Since HIV infects immune cells, when the body tries to turn on the cells to fight the infection it actually ends up propagating the virus. This is how HIV uses the body’s defenses against itself. For a short period of time there is a successful immune response and the virus appears latent, but it is reproducing unabated inside the cells. Eventually the cells die and more viral particles burst forth to infect other cells creating a domino effect. T cells, the immune cells responsible for fighting the infection, are killed while other immune cells, dendritic cells and macrophages, act as reservoirs for replicating virus and transport it to the brain. Loss of T cells occurs for many reasons once the infection takes hold and leads to suppression of the immune system. This is what allows opportunistic infections to occur and ultimately death.

Clinical course of infection

Clinical manifestation ranges from a mild acute illness to severe disease: Early, acute phase – initial normal immune response, 50-70% of adults have this 3-6 weeks after infection, nonspecific symptoms Middle, chronic phase – relative containment, continued HIV replication in CD4+ T cells and macrophages for several years, asymptomatic or minor opportunistic infections Final, crisis phase - the terminal phase of infection, breakdown of host defenses and clinical disease - AIDS